James and the Giant Corn Genetics: Studying the Source Code of Nature

May 11, 2010

Where the superpowers of superweeds come from

Filed under: agriculture,biofortified,Genetics,Plants — Tags: , , — James @ 11:53 am

Superman had the yellow sun of earth, spiderman had a radioactive spider-bite, but what about superweeds, where does their super power (surviving application of Round-up/glyphosate) come from?

To understand how superweeds survive, we first have to understand why normal weeds (the Jimmy Olsens and Lois Lanes of the plant world) die. <– last superhero reference of this post I promise.

Plants are not like people. The list of differences goes on and on, but today the difference we’re concerned about is where amino acids come from. Amino acids are the building blocks of proteins, the same way Adenine (A), Thymine (T), Guanine (G) and Cytosine (C) are the building blocks of DNA. Both our bodies and plants (and almost every other living thing) use the same twenty amino acids to build proteins. Our bodies can make ~12 of the twenty animo acids for themselves, but there are at least eight amino acids that the human body cannot produce (called essential amino acids). Our only source of these amino acids is from protein in our food.

It’s all well and good for us to get amino acids from our food, but plants don’t eat. They’re made of pretty much nothing more than water, sunlight and air. And trust me, none of those things are a good source of protein.

Unlike us, plants have to be able to make all twenty amino acids from scratch. That means they need whole biochemical pathways* that aren’t found in animals. But a biochemical pathway is like an assembly line. Break one of the steps in the middle and the whole thing falls apart. That’s what glyphosate/round-up does.

This part of the story starts with an enzyme called 5-enolpyruvylshikimate-3-phosphate synthase (or EPSPS for short). Do you don’t have to understand what EPSPS does specifically**, what is important is that its job is an important step in making the three amino acids Tryptophan, Phenylalanine, and Tyrosine***.  When EPSPS can’t do its job, the next protein in the biochemical pathway won’t get the parts it needs to do its job, and in short order the whole pipeline shuts down, none of those three amino acids get produced, and the plant dies.

How does glyphosate keep EPSPS from doing it’s job? It imitates one of the the chemical building blocks EPSPS normally works with, so EPSPS proteins will bind to it like they would to the actual chemical compound. But since glyphosate isn’t the compound EPSPS actually work with, it sticks in the protein. If it helps you can think of this as feeding the wrong sort of paper into a printer, causing a paper jam. Lots of individual molecules of glyphosate get into each plant cell. They stick in EPSPS proteins floating within the cell, which keeps EPSPS from doing its job, and once EPSPS stops working, the plant cell can’t make the amino acids it needs to survive, and dies.

Glyphosate is very good at doing what it does: killing plants. And as weed-killers go, it’s a lot less nasty for animals since it works by breaking a protein animals don’t need or even have. But there is one problem. Some weeds are becoming less effected by the herbicide, able to survive larger and large doses.  There are a number of ways plants can evolve to survive large doses of glyphosate. Let’s talk about three:

  1. The first, and probably most obvious, is to change the shape of the EPSPS protein so glyphosate can no longer jam the mechanism. As it turns out mutations that change which amino acid is used at one specific point can produce a version of the EPSPS gene that is less likely to be broken by glyphosate. Think of it as changing the design of a print so paper that would jam the mechanism either won’t fit in the printer at all or passes through harmlessly. This method of getting “superweed” powers has been used by malaysian goose-grass and and australian ryegrass.
  2. A second way for plants to become superweeds is to stop transporting glyphosate around the plant. I don’t have a good printer metaphor for this one. Cells in the leaves of plants are mostly completely grown and don’t need to make as many new proteins as the rapidly dividing cells in meristems and newly developing leaves. When a farmer sprays glyphosate it will mostly land on the mature leaves of the plant. If plants can keep the herbicide in those leaves and keep it from traveling throughout the rest of the plants, they stand a better chance of survival, and that’s exactly what has been found in resistant stiffstalk rye and pigweed.
  3. The first two methods are all well and good, but I probably wouldn’t have bother to write this post if it wasn’t for the method of resistance discovered in Amaranthus palmeri (one of the many species that share the common name pigweed). Palmer amaranth’s approach to resisting glyphosate is charming in its brute force. Resistant plants have duplicated the gene for EPSPS many times (up to 160 copies in some plants!). All those extra genes mean the plants produce a lot more EPSPS protein, so no matter how many individual EPSPSs get jammed by glyphosate molecules, there are still plenty more working EPSPSs to keep doing the job, and the biochemical pathway never stops. Sure a problem with paper jams can be fixed by more advanced printers, or more strict controls on what kind of paper is allowed into the building… but Palmer amaranth’s solution was simply to build a lot more printers.

Potentially there’s potentially a fourth way to develop glyphosate resistance, which would be for the resistant version of the EPSPS protein engineered into glyphosate resistant crops**** to be introgressed into wild relatives allowing those wild crop relatives to become herbicide resistant “super weeds”. This gets talked about a lot and clearly the risk is going to depend on a lot of factors*****. In researching this post I couldn’t find any papers describing herbicide resistant weeds that owe their resistance to a gene from an herbicide resistant crop. And given how much ink has been spilled on the subject, I would expect any such papers to makes a big splash.

*Biochemical pathways are just a bunch of steps needed to get from some molecule an organism already has, to some other molecule the organism wants. Usually each individual chemical change is performed by some specific protein, like workers on an assembly line. (Sometimes its even arranged like an assembly line with intermediate molecules being passed directly from one protein to another, although it isn’t always that way)

**Although if you’re interested you can read more about the details of the EPSPS protein here.

***The first two are certainly essential amino acids. Our bodies can produce our own tyrosine, but all we do is modify phenylalanine. We can’t make it from scratch.

****Weeds that resist glyphosate are “super weeds”, but I can’t imagine ever hearing the crops that resist the exact same herbicide called “super crops” ;).

*****How the crop reproduces, whether its being grown near any wild ancestors, how weedy those wild ancestors are to begin with, which crop alleles are in close linkage with the resistance gene (crop-like traits tend to make weeds much less successful).

Gaines, T., Zhang, W., Wang, D., Bukun, B., Chisholm, S., Shaner, D., Nissen, S., Patzoldt, W., Tranel, P., Culpepper, A., Grey, T., Webster, T., Vencill, W., Sammons, R., Jiang, J., Preston, C., Leach, J., & Westra, P. (2009). Gene amplification confers glyphosate resistance in Amaranthus palmeri Proceedings of the National Academy of Sciences, 107 (3), 1029-1034 DOI: 10.1073/pnas.0906649107

POWLES, S., & PRESTON, C. (2006). Evolved Glyphosate Resistance in Plants: Biochemical and Genetic Basis of Resistance Weed Technology, 20 (2), 282-289 DOI: 10.1614/WT-04-142R.1


  1. That’s a terrific explanation, James. I wonder if we surveyed the people who are most aerated about this topic–I wonder how many of them are certain it is “teh GMO” gene that did it….

    Comment by Mary — May 11, 2010 @ 12:20 pm

  2. Thanks!

    Comment by James — May 11, 2010 @ 2:03 pm

  3. this is all well and good but didn’t the presence of the GMO force selection for the mutation(s)?

    Comment by Keith — May 11, 2010 @ 1:18 pm

  4. Well more specifically, crops genetically engineered to resist glyphosate let farmers use of glyphosate to control weeds on so many more acres and throughout more of the growing season. Which put a lot of selective pressure on the weeds to evolve any sort of resistance.

    I completely agree with you that using a single chemical control isn’t a recipe for long term success, whether it’s an herbicide like glyphosate or an antibiotic like penicillin.

    When glyphosate-tolerant crops were first introduced I doubt anyone expected them to be the only variety available for so many years (we’re only now starting to see new herbicide/resistant-crop systems becoming available to farmers).

    Comment by James — May 11, 2010 @ 1:44 pm

  5. ” I doubt anyone expected them to be the only variety available for so many years ”

    anyone other than Monsanto maybe

    Comment by Keith — May 11, 2010 @ 8:18 pm

  6. When time glyphosate resistant crops were first being introduced Calgene was working on crops resistant to bromoxynil under the brand name BromoTol. There may have been other companies working on other traits as well, but that’s the one I knew about.

    So at least until Calgene went bankrupt I’m quite sure even the people at Monsanto didn’t expected Roundup Ready to have the market to itself for so long.

    Comment by James — May 11, 2010 @ 9:49 pm

  7. Bayer’s Liberty Link/glufosinate resistance trait has been available for a while now, I think – wasn’t it Liberty Link corn that accidentally ended up in Taco Bell shells? And Google News tells me it’s Liberty Link rice that was the problem in the farmer lawsuits. Maybe it was these scandals that prevented this trait from getting a larger market share?

    Comment by Amy — May 12, 2010 @ 11:13 am

  8. Liberty Link/glufosinate crops are definitely starting to show up on the market although I’ve read conflicting things about which crops the trait is commercially available in so far. I know the problem with the Liberty Link rice was that it hadn’t made it through the approval process yet, which was the same problem that the StarLink corn that showed up in taco shells back in the day had, although StarLink corn was just another variety insect resistant bt corn (made by another company that later went bankrupt and actually ended up getting bought by Bayer)

    Comment by James — May 12, 2010 @ 11:51 am

  9. right, Star Link! Thanks for jogging my memory on that one. the timeline didn’t quite match up there.

    Comment by Amy — May 12, 2010 @ 6:05 pm

  10. Nice post James!

    The journal club I almost never go to recently read a good review article about potential introgression of GM genes into weed species (Stewart et. al., Nature Reviews Genetics 4, 806-817). In short, the authors state that some crops may be at more risk than others because of the presence of close relatives that are also weeds. The article also reviews some techniques that could be used to reduce the chance of introgression, like linking the resistance gene with another that reduces reproductive fitness. It didn’t seem that pigweed was a particularly close relative of any crop species, so introgression seems unlikely.

    Interestingly, I would think that for organic farmers, herbicide resistance in weeds would be of no concern at all, since they don’t use herbicides. Of more concern might be insect resistance weeds, since they have increased fitness against any competitor.

    Thanks for the detailed explanation of resistance mechanisms though, I glanced at the paper you linked but had not read it fully yet. Now I don’t have to 🙂

    Comment by Sanjuro — May 11, 2010 @ 1:40 pm

  11. I should thank you! Your question inspired me to write this post, though it took a while to pull it all together.

    I’ll definitely take a look at the review you mention. Like I said in the post, herbicide resistance getting into weedy relatives is definitely an issue people think about a lot, because it really does have the potential to be a problem if people don’t keep it in mind. For example, engineering sorghum (Sorghum bicolor) to be herbicide resistant probably would be a bad idea (as much as I love that crop and its genome), because a close relative johnson grass (Sorghum halepense) is a problematic weed in large parts of the world.

    Comment by James — May 11, 2010 @ 1:49 pm

  12. also, buried in this article about the dupont/monsanto lawsuit is the story of how the RR gene was discovered – http://money.cnn.com/2010/05/06/news/companies/monsanto_patent_full.fortune/

    as well as a good explanation regarding RR vs GAT

    Comment by Amy — May 12, 2010 @ 11:18 am

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